CVD are the main critical healthiness complication of the worldwide and their outcomes have been reported as an out of every three deaths in the United States[16]. While remarkable scientific attempts has been straighten to identifying bimolecular functions regulating the beginning and developing of disease, much remains controversial[17]. One of the important and useful remedy option for subjects with acute coronary syndrome is the PCI that can be main way for improving in patients with coronary artery anomalies. However some complications such as myocardial injury due to PCI were reported that causing to impecunious prognosis[18]. According to the current investigations antioxidant and anti-inflammatory properties of polyphenols have been detected[19]. Turmeric has a main polyphenol ingredient called curcumin that is obtainable as an over-the-counter (OTC) supplement widespread of world[20]. This randomized, controlled trial assessed the effects of curcumin and nano-curcumin in the in patients undergoing coronary elective angioplasty. The results showed a significant effect of curcumin and nano-curcumin on lipoid profile, stress oxidative indices and inflammatory markers. Several studies have investigated the effect of curcumin oral intake in cardiovascular diseases and some of which are consistent with the present study and some contradict it. The results of some other studies indicate the anti-sclerotic property of curcumin[21, 22].
The results of Chuengsamarn S et al. study regarding the use of curcumin supplementation on coronary artery disease also showed a significant decrease in plasma TG concentration in the intervention group, which was consistent with the present study[23]. However, in a study by Baum L et al. in 2007, consumption 1 and 4 grams of curcumin daily for 6 months did not show any significant changes in lipid profiles[24]. In order to justify the results of this study, in addition to the low sample size, supplementation of curcumin has no effect in healthy subjects with normal lipid profile.
Also, results of Adibian et al. study showed that daily supplementation with 1500 mg curcumin for 10 weeks reduced serum concentration of triglyceride in the intervention group compared to the baseline. But the mean serum concentrations of total cholesterol, LDL-C, and HDL-C had no significant change at the end[25]. The cause of the no changes in serum levels of some of the lipid profile components in this study is that not all participants were hyperlipidemia. In addition, there is a low bioavailability of curcumin, which metabolism is fast in the body and its systematic elimination occurs[26]. Regarding the cholesterol-lowering mechanism by curcumin, a hypothesis has been clarified in animal studies, which is also an involving effect of curcumin on inhibition of dietary cholesterol absorption and consequent reduction of serum cholesterol[27]. For this fact, several mechanisms have been introduced. Stopping in micelle development, stimulating fecal excretion of total steroids and bile acids are examples of these mechanisms. Increasing of bile acids excretion resulted in more conversion of cholesterol to bile acids. This fact, cholesterol conversion bile acids, is the main pathway of cholesterol elimination and accounts for about 50% of daily cholesterol excretion[28].
The another possible mechanism of curcumin in improving dyslipidemia improves cholesterol catabolism by enhancing the activity of the cholesterol 7 hepatic hydroxylase enzyme, which inhibits the synthesis of cholesterol by inhibiting the HMGCOA reductase enzyme[29]. Enhancing of the expression of hepatic CYP7A1 gene by curcumin consumption, resulted in reducing the blood cholesterol levels and approved the hypocholesterolemic properties of curcumin[30]. Expression of AMP-activated protein kinase and peroxisome proliferator-activated receptor boosted by curcumin that affected energy metabolism of subcutaneous adipocyte tissue in mice that treated with curcumin-supplemented high fat diet[31].
Interestingly, although curcumin shows antioxidant properties by supplying hydrogen radicals and scavenging free radicals, there are a growing number of evidences that it can act as pro-oxidant under certain condition by generating ROS[32]. Results of our study indicated that curcumin supplementation improved status of oxidative stress. In this study intake of curcumin and nano-curcumin increased the mean of TAC, SOD and GSH-Px, also plasma MDA significantly decreased in the intervention groups. Results of Banaeifar et al. study demonstrated that Eight weeks consumption of curcumin caused a significant increase on the level of SOD and GSH-Px enzymes in the rats[33]. Also the results of Quiles et al. showed that curcumin reduces oxidative stress and lipid peroxidation and attenuates aortic fatty streak development in rabbits that treated with atherogenicity diets[34]. According to the Alizadeh F and et al. scientific report, 10 weeks of curcumin nanomicelle supplementation resulted in a statistically significant improvement in plasma levels of TAC, MDA, CRP and TNF-α in comparison to the placebo in asthenoteratospermia patients[35].
Immoderate ROS generation has a main role in the beginning, developing and clinical outcomes in CVD. Although many studies have been done and considerable development and advances occurred in field of free radical biology and cardiovascular treatment, but main mechanisms of CVD and outcomes of pathophysiologically increased ROS in cardiovascular tissue not fully understood[7]. Nuclear factor kappa B (NF-κB) signaling pathway activated with ROS. NF-κB proteins are a subset of transcription factors that manage the expression of genes affiliated with inflammation. According the scientific results, ROS can control the activation and inhibition of NF‐κB‐signaling. Protecting versus over generation of free radicals in body can occur with superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), as an anti-oxidant enzymes cooperatively with the nonenzymatic system such as glutathione and vitamins (A, C, and E)[5].
Anti-oxidant properties of curcumin have been greatly researched. This polyphenol can inhibit ROS degradation and also reduce inflammatory factors through down regulation of pro-inflammatory cytokines and transcription factors[29]. Scientific research has also paid great attention to the immunomodulatory role of curcumin. In this regard, activity of immune system cells such as T-cells, B-cells, macrophages, neutrophils, natural killer (NK) cells, and dendritic cells are regulated with curcumin. Also, curcumin, at low doses, may boost antibody responses. These molecular affirmations propose that its detailed beneficial effects could be because of direct anti-oxidative and anti-inflammatory properties, additionally in part to its capacity to control the immune systems[26, 20].
Curcumin inhibits the production of active oxygen species. It linked to thyroxin reductase and turns it to nicotine amide dinucleotide phosphate oxidase (NADPH oxidase) which prevents from ROS formation. Also it increases glutathione gene expression and through iron binding it can do its antioxidant role[36]. Results of this study indicated that inflammatory biomarkers levels were significantly decreased in the intervention groups. Curcumin has suppressive effect on production of the inflammatory cytokine TNF- α, which in turn leads to inhibition of NF-KB being responsible for promoting intracellular inflammation. It down regulates various pro-inflammatory cytokine expressions such as TNF-α, interleukins (IL-1, IL-2, IL-6, IL-8, IL-12) and chemokines, most likely through inactivation of the nuclear transcription factor, nuclear factor (NF)-κB[37].
This randomized, controlled trial was the first study that studied and compared the effects of curcumin and nano-curcumin in the in patients undergoing coronary elective angioplasty. The results of this research have been statistically reported and discussed. Distinctly, to explain the clinical relevance of these data, more investigations with larger sample size, different doses and longer duration are required. Also, because of owing to budget limitations we were not able to measure other biomarkers such as ROS radicals and some important inflammatory factors.